In light of the shortage of donor organs available for transplantation, cross-species transplantation has been considered as an alternative to allotransplantation. However, xenografts undergo hyperacute rejection within minutes to hours after transplantation in untreated recipients. Natural and induced xenophilic antibodies are held to be responsible for hyperacute and acute rejection of xenogeneic organs. But hyperacute graft rejection has been absent when neonatal porcine hearts are transplanted into non-immunosuppressed newborn baboons. Therefore it appears that the low levels of natural xenophile antibodies in the newborn infant may permit prolonged xenograft survival. In this study, four newborn rhesus monkeys 3-4 weeks old received neonatal outbred swine (24-48 hours old) cardiac transplants which were grafted to the abdominal aorta and vena cava. Intensive perioperative cardiorespiratory monitoring and support was instituted in an effort to sustain these recipients during the immediate post-transplant period. Three of the four grafts achieved normal contractility after reperfusion with one graft failing presumably due to hypoperfusion. The graft survival times were approximately 45 minutes, 1 hour 30 minutes, and 4.5 hours. Graft failure was secondary to animal death during the immediate postoperative period and did not appear to be due to hyperacute rejection. These preliminary results suggest that although hyperacute rejection is not seen in neonatal swine-to-monkey xenotransplantation, it is difficult to maintain the recipient despite aggressive monitoring and perioperative support. We are currently analyzing serum samples and cardiac biopsies (graft and native heart) taken from all subjects to determine what, if any, immunologic injury was incurred in the grafts. It appears that the gross disparity between the comparatively large swine hearts and small recipients was the principal cause of animal death. Alternatively, an acute inflammatory process after xenografting may have been contributory.